Undirected Deuteration of Arenes Based on DCL™
Background & Overview
Isotopically-labeled compounds have a wide range of applications, and such diverse applications have fueled continued interest in developing convenient and robust synthetic methods. Complex aromatic scaffolds exist in many biologically active molecules and related compounds, therefore, the incorporation of deuterium into these aromatic scaffolds is a crucial part of deuterated technology.
Existing Strategy for the Synthesis of Undirected Deuteration of Arenes
Methods for deuteration of aromatic hydrocarbons include pH-dependent methods, in which incorporation of deuterium is achieved through the use of Bronsted/Lewis acids; and methods of base-mediated H/D exchange reactions are also known. Due to harsh reaction conditions, these methods are often used for simple aromatics. In addition, although transition metal-catalyzed reactions can achieve high activity, they face challenges such as undesired side reactions. For example, hydrogen isotope exchange of arylthioanthene salts using a homogeneous molecular palladium catalyst and deuterium-tritium gas. Using this protocol, deuterium and tritium atoms are introduced into drug molecules with high isotopic purity, and the reaction pathway is shown in Fig. 2.
Fig.1 Deuteration of aryl thianthrenium salts using molecular palladium catalyst.[3]
Fig.2 Plausible mechanistic pathway for deuteration of aryl thianthrenium salts.[3]
DCL™ in Undirected Deuteration of Arenes
BOC Sciences has established a hydrogen isotope exchange method for aromatic C-H bonds. Our DCL™ technology platform is focused on addressing the non-directed deuteration of drug molecules and other similarly complex aromatic scaffolds. The catalyst system we used has broad functional group tolerance and enables high H/D exchange of aromatic moieties under very mild conditions. Our method is broadly applicable to both electron-rich and electron-poor aromatics. We anticipate that our DCL™ will be proven to be useful for isotopic labeling in various fields to meet your diverse range of service needs, from mechanistic research to drug development.
Intellectual Property Protection
BOC Sciences has always regarded intellectual property as the most valuable asset of the company and its customers. We have signed non-disclosure agreements with customers and employees before the project starts, and provide synthetic route design and synthesis services in strict accordance with the terms of the non-disclosure agreement, striving to provide customers with target compounds in the shortest time possible.
References
- Atzrodt J, et al. C-H functionalisation for hydrogen isotope exchange. Angewandte Chemie International Edition. 2018, 57(12): 3022-3047.
- Farizyan M, et al. Palladium-Catalyzed Nondirected Late-Stage C–H Deuteration of Arenes. Journal of the American Chemical Society. 2021, 143(40): 16370-16376.
- Prakash G, et al. C-H deuteration of organic compounds and potential drug candidates. Chemical Society Reviews. 2022.
